Abstract
Background: Children presenting with chronic liver disease or acute liver failure often have an underlying genetic disorder. The aim of this study was to analyze the clinical and genetic spectra of inherited liver disease in children in a tertiary hospital.Methods: A total of 172 patients were classified into three groups according to their clinical presentation: cholestasis (Group A), liver enzyme elevation (Group B), and hepato/splenomegaly (Group C). Next-generation sequencing (NGS) was performed on all patients recruited in this study. The genotypic and phenotypic spectra of disease in these patients were reviewed.Results: The median age at enrollment of the 172 patients was 12.0 months (IQR: 4.9, 42.5 months), with 52.3% males and 47.7% females. The overall diagnostic rate was 55.8% (96/172) in this group. The diagnostic rates of whole-exome sequencing (WES) and targeted gene panel sequencing (TGPS) were 47.2% and 62.0%, respectively (no significant difference, p = 0.054). We identified 25 genes related to different phenotypes, including 46 novel disease-related pathogenic mutations. The diagnostic rates in the three groups were 46.0% (29/63), 48.6% (34/70), and 84.6% (33/39). ATP7B, SLC25A13, and G6PC were the top three genes related to monogenic liver disease in this study.Conclusion: WES and TGPS show similar diagnostic rates in the diagnosis of monogenic liver disease. NGS has an important role in the diagnosis of monogenetic liver disease and can provide more precise medical treatment and predict the prognosis of these diseases.
Highlights
Children with chronic liver disease or acute liver failure often have underlying genetic disorders that caused by liver-based diseases and systemic diseases [1]
The diagnostic algorithm was as follows: first, liver diseases caused by biliary atresia, infection, drug hepatotoxicity, autoimmune hepatitis (AIH), and alcohol liver disease were excluded according to the history, physical examination and initial workup for viruses, bacteria and autoantibodies associated with autoimmune diseases
Patients with suspected genetic diseases such as Alagille syndrome (AS), Wilson disease, glycogen storage disease (GSD), progressive familial intrahepatic cholestasis (PFIC), bile acid metabolic disease, and citrin deficiency were studied via targeted gene panel sequencing (TGPS) or whole-exome sequencing (WES), and patients without suspected genetic diseases were studied via WES
Summary
Children with chronic liver disease or acute liver failure often have underlying genetic disorders that caused by liver-based diseases and systemic diseases [1]. Liver diseases caused by gene mutations are defined as inherited liver diseases or monogenic liver diseases. These diseases often present with overlapping phenotypes and lack specific laboratory testing indicators, which may lead to delays in diagnosis and improper treatment. The aim of this study was to analyze the clinical and genetic spectra of inherited liver diseases in children by using WES and TGPS, and to compare the diagnostic yield of these two methods in a tertiary hospital in China. The aim of this study was to analyze the clinical and genetic spectra of inherited liver disease in children in a tertiary hospital
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